Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR-146a-5p and regulating TRAF6 expression

Abstract

Intervertebral disc degeneration (IDD) is associated with the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. Emerging studies have shown that long noncoding RNAs (lncRNAs) play critical roles in the development of IDD. Using bioinformatics prediction, we hereby sought to identify the lncRNAs that regulate the expression of microRNA-146a-5p (miR-146a-5p), an IDD-related inflammatory factor. Our study demonstrated that lncRNA HCG18 acted as an endogenous sponge to down-regulate miR-146a-5p expression in the NP cells by directly binding to miR-146a-5p. In addition, HCG18 expression was up-regulated in the patients with IDD, bulging or herniated discs, and its level was positively correlated with the disc degeneration grade. In vitro, miR-146a-5p up-regulation HCG18 retarded the growth of NP cells by decreasing S phase of cell cycle, inducing cell apoptosis, recruitment of macrophages and hypercalcification. Conversely, down-regulation of miR-146a-5p exerted opposite effects. Furthermore, we elucidated that TRAF6, a target gene by miR-146a-5p, was modulated by HCG18 expression. Restore of TRAF6 expression by virus infection reserved the effect of HCG18 on the NP cells. Altogether, our data indicated that HCG18 suppressed the growth of NP cells and promoted the IDD development via the miR-146a-5p/TRAF6/NFκB axis.

The long non‐coding RNA HCG18 promotes the growth and invasion of colorectal cancer cells through sponging miR‐1271 and upregulating MTDH/Wnt/β‐catenin

“…Herein, our study reveals, for the first time, a crucial role of lncRNA HCG18 in colorectal cancer. HCG18 has been reported to regulate the proliferation, cell cycle, and apoptosis of nucleus pulposus cells during the progression of intervertebral disc degeneration . Notably, HCG18 was recently identified as a novel cancer‐related lncRNA.…”

“…HCG18 has been reported to exert its function by acting as a competing endogenous RNA to sponge miRNAs, such as miR‐146a‐5p and miR‐34c‐5p . Herein, we aimed to identify the downstream target miRNA of HCG18 in colorectal cancer by bioinformatics analysis.…”

“…HCG18 has been reported to regulate the proliferation, cell cycle, and apoptosis of nucleus pulposus cells during the progression of intervertebral disc degeneration. 36,37 Notably, HCG18 was recently identified as a novel cancer-related lncRNA. Decreased HCG18 expression is found in patients with anaplastic gliomas and has prognostic value.…”

LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

“…Recently, accumulating evidence has strongly implied that ceRNA hypothesis has been extensively proposed in IDD. For example, lncRNA hickson compact group 18 (HCG18) upregulated the expression of 146a‐5p target gene tumor necrosis factor receptor‐associated factor 6 (TRAF6) through competitively sponging miR‐146a‐5p to suppress the growth of NP cells and promote the IDD development . Moreover, lncRNA H19 functioned as a ceRNA for miR‐22 and led to the derepression of its target lymphoid enhancer factor 1 (LEF1) for regulating NPC senescence and proliferation, and ECM synthesis .…”

LncRNA‐RMRP promotes nucleus pulposus cell proliferation through regulating miR‐206 expression

“…Inhibited expression of TUG1 inhibited the expression of β‐catenin, Bax, ADAMTS5, MMP3, Caspase‐3 and Wnt1 and promoted the COL2A1, Aggrecan and Bcl‐2 expression. Xi et al demonstrated that the expression of HCG18 was up‐regulated in IDD patients and higher expression of HCG18 was correlated with the grade of disc degeneration. In addition, they showed that HCG18 inhibited NP cell growth and enhanced the development of IDD through the NFκB/TRAF6/miR‐146a‐5p axis.…”